Right thyroid lobe agenesis and left thyroid colloid benign nodule discovered incidentally in female with breast carcinoma receiving chemotherapy for multiple metastases: Case report and review of the literature

Introduction and importance Thyroid hemiagenesis (THA) is the failure of embryologic development of a lobe of the thyroid gland and is a rare anomaly of uncertain incidence. The left lobe is more commonly absent than the right lobe. It is discovered incidentally during investigations. Case presentation A 48 year old Egyptian female presented at the thyroid surgery clinic at our institution to follow up after a nodule left thyroid lobe accidently discovered on positron emission tomography (PET) scan undertaken to follow up on bone metastasis of breast cancer which was surgically removed about 14 years ago. Clinical discussion The patient looked clinically well with no scar in the anterior of the neck, no palpable thyroid nodules, and no lymphadenopathy. Ultrasound imaging of the neck revealed absent right thyroid lobe tissue and a nodule was noted at the upper pole of the left thyroid. Laboratory tests unremarkable, with TSH (2.14 mIU/L), and FT4 (12.4 pmol/L) within normal range. Fine needle aspiration and cytology of the thyroid nodule revealed atypia of undetermined significance. Conclusion THA is rare and right THA is even rarer. It is usually asymptomatic, and diagnosis is mostly incidental while investigating symptoms due to pathology of the other thyroid lobe or any of the parathyroid glands. In much rarer circumstances, right THA might be discovered when investigating conditions not related to the thyroid or parathyroid glands years after the initial pathology as in the current case. Etiology is inconclusive but genetic factors could play a role. No treatment is required if no symptoms are present.


Introduction
The thyroid is one of the largest glands weighing approximately 15-20 g in normal adults [1]. The two hormones it secretes influence almost every organ system in the body and play important roles in organ development and in homeostatic control of essential physiological mechanisms such as body growth and energy expenditure [1,2]. Thyroid hormone secretion is regulated via the hypothalamic-pituitary-thyroid axis [1].
Thyroid hemiagenesis (THA) is the failure of embryologic development of a lobe of the thyroid gland and is a rare anomaly of uncertain incidence [3]. The left lobe is absent in 80 % of cases, the right is in 20 % of cases (left to right hemiagenesis ratio of 4:1), and the isthmus in 50 % of patients [3]. Most reported cases are female with the left thyroid lobe absent [4]. Most cases are sporadic, however familiar clusters have been documented [5]. THA is usually associated with normal thyroid function [5], where patients have absent thyroid lobe, with contralateral lobe in euthyroid state without abnormalities [3]. Nevertheless, a range of pathologies have been observed in the remaining thyroid tissue in THA, including hyperthyroidism, multinodular goiter, hypothyroidism, benign adenoma, adenocarcinoma, and Grave's disease [3]. Most THA patients report no symptoms, and the condition is discovered incidentally during investigations or intraoperatively [5]. As for management, THA patients risk developing supplementary thyroid pathologies and may advantage from l-thyroxine treatment to lower the thyrotropin levels to those of the normal population [6]. Further research is required to observe if such interference early in life would stop development of associated thyroid problems [6].
We report a 48 Egyptian female with right thyroid hemiagenesis seen at our institution. She had mastectomy for a left primary breast cancer 13 years ago. She had no thyroid complaints, and ultrasound (US) imaging of the neck confirmed absent right thyroid lobe tissue. We report this case in line with the updated consensus-based surgical case report (SCARE) guidelines [7].

Presentation of case
A 48 year old Egyptian female presented at our institution on July 2018 to follow up a nodule in the left thyroid lobe that was accidently discovered in positron emission tomography (PET) scan being done as follow up for her breast cancer. She had complained of neck fullness and choking. There was no previous thyroid surgery and no family history of thyroid disease. She did not consume alcohol and was a non smoker. In 2009, she was diagnosed with left breast cancer in Egypt (stage T3 N2 M0), managed by mastectomy, axillary clearance, then by chemotherapy and radiotherapy. In November 2012, she presented at our institution in Doha with bone metastasis. She was started on hormonal therapy.
Upon physical examination, the patient looked clinically well with no visible scar in the anterior aspect of the neck, no palpable thyroid nodules, and no lymphadenopathy. She was conscious and alert, there was no exophthalmos, and systems examination was unremarkable. Her laboratory tests were unremarkable, with TSH (2.14 mIU/L), and FT4 (12.4 pmol/L) within normal range. Ultrasound (US) imaging of the neck revealed absent right thyroid lobe tissue (Fig. 1). Left thyroid measures 17 mm with normal vascularity. An isoechoic complex nodule was noted at the upper pole (14 mm × 12 mm). There were no pathologic enlarged lymph nodes.
Because of previous history of metastasis from her breast cancer, FNA evaluation was advised and undertaken. Fine needle aspiration and cytology (FNAC) of the thyroid revealed atypia of undetermined significance (AUS). The case was discussed at our thyroid multidisciplinary team (MDT) meeting, and the recommendation was to follow-up by US after 6 months.
The patient was followed up for 4 years with US neck undertaken on January 2019, and then February and July 2021. The US scans revealed slightly increased size of the left thyroid nodule and confirmed the absence of the right thyroid lobe. US neck in November 2021 showed a well-defined solid heterogenous predominantly mildly hypoechoic nodule (ACR TR4) in the lower left lobe measuring about 20 mm (previously 18 mm).
Fine needle aspiration and cytology (FNAC) were undertaken for the nodule on February 2021 and October 2022. Both revealed follicular cells and abundant colloid in a background of blood. There were no atypical or malignant cells seen. The patient had PET scan on September 2021 that showed stable appearance of hypermetabolic left thyroid lobe nodule without any significant interval change. Tracer uptake in the head and neck region was physiologic, and there was no nodal hypermetabolism or cervical adenopathy. There was no apparent abnormal cerebral FDG uptake. The patient also developed a liver nodule that was discovered during a PET scan on January 2021 that revealed a newly developed 1.7 cm metabolic diameter. There was fluorodeoxyglucose (FDG) accumulation in Segment VII of the liver close to diaphragmatic surface.
The patient also had US guided biopsy from the supraclavicular neck lymph nodes on February 2021 that revealed metastatic carcinoma with features suggestive of a breast primary (Fig. 2). Our recommended plan was to follow up the thyroid nodule with US and FNA to ensure there was no malignant cells.

Discussion
Thyroid Hemiagenesis (THA) is a rare congenital anomaly [5], and right THA is even rarer. We report a 48 year old Egyptian female with right THA discovered incidentally at our institution. We also report the findings of the literature review of right thyroid hemiagenesis case reports that we undertook, where we summarize the characteristics of the reported cases that were identified.
As for demography, our literature review (Table 1) shows that the age range of right-sided THA cases varied from 18 years [8] to 66 years [9]. However, many cases were observed in individuals between 30 and 58 years of age. Our patient's age was 48 years, falling within the age range reported by others [10][11][12][13]. In terms of sex, THA is seen more often among females (female to male ratio 3:1) [9,13], in support of our case who was a female. Table 1 also shows that females were more common, with a female to male ratio 5.5:1. THA, especially on the right side, may be influenced by sex-related factors similar to those in patients with an ectopic thyroid gland [13].
In terms of geographical distribution of right-sided THA, Table 1  depicts that 4 of the14 cases we identified where in Japan (28.5 %). In a Japanese study of 151,374 male and 148,534 female subjects, THA was detected in 0.016 % and 0.027 % of the sample respectively [13]. In the same study, the prevalence of right THA (12 subjects) was significantly lower than that of left hemiagenesis (p < 0.001) [13]. Another study in Turkey reported THA prevalence of 0.25 % in an outpatient referral population and 0.025 % in a normal population [21]. Table 1 shows that THA is also observed in many other parts of the globe. As regards to location, the left lobe is absent in 80 % of cases and the right lobe is absent in 20 % of cases [3]. Hence, THA is more commonly seen on the left side, with ratio 4:1 [9]. Systematic ultrasound evaluation confirmed the female predominance and higher incidence of left THA [22]. Hence, our literature review focused on the rarer cases of right THA for which we identified 14 cases. To the best of our knowledge, we are not aware of any similar cases published in the North Africa and Arabian Gulf region.
Pertaining to diagnosis, patients with THA are usually asymptomatic and generally discovered incidentally. Most published cases of THA generally and of right THA in particular have been observed incidentally after patients were examined for thyroid or parathyroid conditions [14,19]. In agreement, Table 1 shows that all the cases were discovered incidentally when investigations were undertaken to investigate contralateral lobe pathology. Less frequently, THA is discovered when investigating a non-thyroid condition such as the current case, where the patient was being followed up for bone metastasis after breast cancer. Only then, a PET scan confirmed that the right thyroid lobe was absent. THA per se usually does not cause complaints by itself [21], and the first systematic ultrasound evaluation of THA in normal children confirmed a 0.2 % prevalence [22].
In connection with etiology, members of the PAX family are required for cell growth and differentiation in fetal tissues [23]. Consequently, PAX8 participates in regulation of embryogenesis of the thyroid gland [23]. PAX8 gene belongs to the paired-box (PAX) family of nine transcriptional factors (PAX1-9) [24]. It was observed in the single lobe of THA and it was not present in the other thyroid side [23]. However, others noted that the candidate gene Pax8 may not be a key genetic factor in THA and that other genes may be involved [6].
In terms of associated pathologies with THA, Table 1 shows that 3 of the 14 cases had right side parathyroid pathologies, and all cases had left thyroid lobe pathology. A study of patients with thyroid disorders found 12 cases with thyroid hemiagenesis (0.25 %) [21].
As for management, none is required if patient is euthyroid.  However, follow up and investigations are needed to discover any associated thyroid or parathyroid abnormalities that should then be managed accordingly.

Conclusion
THA is rare and right THA is even rarer. It is usually asymptomatic, and diagnosis is mostly incidental. In much rarer circumstances, THA might be discovered when investigating conditions not related to the thyroid or parathyroid glands, which in the present case, was left breast cancer. Etiology is inconclusive. No treatment is required if no symptoms are present. Further research to investigate the incidence of THA in general and particularly right THA are required, as well as the potential etiology of such cases.

Consent
Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal on request.